Amyotrophic Lateral SclerosisPhase 2NCT01777646
Autologous Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF in people with Amyotrophic Lateral Sclerosis, run by Brainstorm-Cell Therapeutics at 1 site in Israel.
Trial summary
The study will evaluate the safety, tolerability and therapeutic effects of transplantation of escalating doses of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), in patients with amyotrophic lateral sclerosis (ALS). Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2012to Sep 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must fulfill El Escorial criteria (APPENDIX 2) for definite or probable ALS (sporadic and not familial)
- Participants, either men or non pregnant women are between 20 and 75 years of age.
- The patient is mentally intact and psychologically stable
- Patients will be with an ALS-FRS-R scale (APPENDIX 3) of at least 30 and disease duration of less than 2 years.
- Patient has sufficiently bulky muscles.
- Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.
Who cannot join
- Patient has a positive test for HBV, HCV or HIV.
- Patient has high protein in the CSF (Protein > 70 mg/ml).
- Patient has lymphocytosis in the CSF (lymphocytes > 5/ml).
- Patient is positive for anti-GM1 antibodies.
- Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
- The patient is a respiratory dependent patient.
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- Patients with renal failure (Cr > 2 mg/dl).
- Patients with impaired hepatic function (ALT, AST or GGT 2-fold higher than normal upper limit).
- Patients suffering from significant cardiac disease, malignant disease or any other disease that may risk the patient or interfere with the ability to interpret the results
- Patient with active infections.
- Participation in another clinical trial within 1 month prior to start of this study.
- Patient has not been treated previously with any cellular therapy.
- Subject unwilling or unable to comply with the requirements of the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIa, Open Label, Dose-escalating Clinical Study to Evaluate the Safety, Tolerability and Therapeutic Effects of Transplantation of Autologous Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS).
The study will evaluate the safety, tolerability and therapeutic effects of transplantation of escalating doses of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), in patients with amyotrophic lateral sclerosis (ALS).
Read the detailed description
This is a phase IIa prospective, open label, dose-escalating, three patient-group clinical study, to evaluate the safety, tolerability and preliminary efficacy of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a potent treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early disease stages. This study is a single center trial. It is anticipated that the study will be conducted at the Department of Neurology \& Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem in Israel. In addition, ALS patients could also be referred to the clinical site above by other medical centers.
All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage ALS disease with duration of less than 2 years. ALS patients identified as "predisposed" will be approached and requested to sign an Informed Consent Form (ICF). Overall, 14 patients will be recruited.
Treatment will start with the lowest dose (94x106 cells) and the dose will be increased to the next medium and high dose (141x106 and 188x106 respectively), for the next patients group only following safety analysis.
The expected duration of patient screening period prior to enrollment into this study is in-between two weeks up to 2 days prior to the study enrollment day during visit 2 (verification of compliance with inclusion/exclusion criteria including clinical laboratory results). Eligible patients will be enrolled into the study and will be observed for every month during a "run in period" of 3 months for determination of the progression rate of the disease (allowing a time window of ± 5 days for all visits). During the "run in period" after about 6 weeks following enrollment, patients of both study groups will undergo a Bone Marrow Aspiration (BMA) procedure and MSC-NTF cells will be produced from the bone marrow aspirate based on Brainstorm Cell Therapeutics Ltd proprietary method. On the last "run in period" visit, patients will undergo the treatment and MSC-NTF will be transplanted by IM+IT to the early ALS patients.
After the MSC-NTF transplantation patients will be observed on a monthly basis for a post treatment follow up period of 6 months (allowing a time window of ± 5 days for all visits). Treatment safety, adverse events and exploratory parameters, to establish ALS progression rate assessment of the disease will be recorded throughout the duration of the "run in period" and the post treatment follow up period.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF
- Keywords
- Mesenchymal Strmal Cells (MSC), Amyotrophic Lateral Sclerosis (ALS), Neuroprotection, Neurodegeneration, Stem cells
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSFBiological
| Study group | Role | What they receive |
|---|---|---|
| MSC-NTF | Experimental | Not described Receives: Biological: MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety evaluation and tolerability of a single treatment administration in an escalating-dose of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF)
Measured: At baseline and up to 6 month following treatment administration
Secondary outcomes (5)
Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale
Measured: At baseline and up to 6 month following treatment administration
Changes in muscle strength grading (MVIC) by muscle chart
Measured: At baseline and up to 6 month following treatment administration
Changes in muscle bulk estimated by MRI of the upper and lower extremities
Measured: At baseline and up to 6 month following treatment administration
Change in upper and lower extremities circumference (cm)
Measured: At baseline and up to 6 month following treatment administration
Changes in EMG parameters
Measured: At baseline and up to 6 month following treatment administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study startDec 2012
- Primary completionSep 2014
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brainstorm-Cell Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Responsible party
- Sponsor
- Investigators
- Dimitrios Karusis, MD, PhD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01777646
- Sponsor's protocol ID
- MSC-NTF-002-HMO-CTIL
- Status last verified
- Mar 2018
- First submitted
- 12 Dec 2012
- Last updated
- 8 Mar 2018
- Results posted
- No
Publications
Gothelf Y, Kaspi H, Abramov N, Aricha R. miRNA profiling of NurOwn(R): mesenchymal stem cells secreting neurotrophic factors. Stem Cell Res Ther. 2017 Nov 7;8(1):249. doi: 10.1186/s13287-017-0692-1.
PubMed 29116031Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, Vaknin-Dembinsky A, Ben-Hur T, Offen D, Abramsky O, Melamed E, Karussis D. Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. JAMA Neurol. 2016 Mar;73(3):337-44. doi: 10.1001/jamaneurol.2015.4321.
PubMed 26751635
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa, Open Label, Dose-escalating Clinical Study to Evaluate the Safety, Tolerability and Therapeutic Effects of Transplantation of Autologous Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS).
- ClinicalTrials.gov ID
- NCT01777646
- Acronym / sponsor ID
- MSC-NTF-002-HMO-CTIL
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Mesenchymal Strmal Cells (MSC), Amyotrophic Lateral Sclerosis (ALS), Neuroprotection, Neurodegeneration, Stem cells
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Brainstorm-Cell TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Study start
- Dec 2012 (actual)
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 29 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will evaluate the safety, tolerability and therapeutic effects of transplantation of escalating doses of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), in patients with amyotrophic lateral sclerosis (ALS).
Detailed description
This is a phase IIa prospective, open label, dose-escalating, three patient-group clinical study, to evaluate the safety, tolerability and preliminary efficacy of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a potent treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early disease stages. This study is a single center trial. It is anticipated that the study will be conducted at the Department of Neurology \& Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem in Israel. In addition, ALS patients could also be referred to the clinical site above by other medical centers.
All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage ALS disease with duration of less than 2 years. ALS patients identified as "predisposed" will be approached and requested to sign an Informed Consent Form (ICF). Overall, 14 patients will be recruited.
Treatment will start with the lowest dose (94x106 cells) and the dose will be increased to the next medium and high dose (141x106 and 188x106 respectively), for the next patients group only following safety analysis.
The expected duration of patient screening period prior to enrollment into this study is in-between two weeks up to 2 days prior to the study enrollment day during visit 2 (verification of compliance with inclusion/exclusion criteria including clinical laboratory results). Eligible patients will be enrolled into the study and will be observed for every month during a "run in period" of 3 months for determination of the progression rate of the disease (allowing a time window of ± 5 days for all visits). During the "run in period" after about 6 weeks following enrollment, patients of both study groups will undergo a Bone Marrow Aspiration (BMA) procedure and MSC-NTF cells will be produced from the bone marrow aspirate based on Brainstorm Cell Therapeutics Ltd proprietary method. On the last "run in period" visit, patients will undergo the treatment and MSC-NTF will be transplanted by IM+IT to the early ALS patients.
After the MSC-NTF transplantation patients will be observed on a monthly basis for a post treatment follow up period of 6 months (allowing a time window of ± 5 days for all visits). Treatment safety, adverse events and exploratory parameters, to establish ALS progression rate assessment of the disease will be recorded throughout the duration of the "run in period" and the post treatment follow up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MSC-NTF | Experimental | Biological: MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient must fulfill El Escorial criteria (APPENDIX 2) for definite or probable ALS (sporadic and not familial)
- Participants, either men or non pregnant women are between 20 and 75 years of age.
- The patient is mentally intact and psychologically stable
- Patients will be with an ALS-FRS-R scale (APPENDIX 3) of at least 30 and disease duration of less than 2 years.
- Patient has sufficiently bulky muscles.
Key exclusion criteria (13 listed)
- Patient has a positive test for HBV, HCV or HIV.
- Patient has high protein in the CSF (Protein > 70 mg/ml).
- Patient has lymphocytosis in the CSF (lymphocytes > 5/ml).
- Patient is positive for anti-GM1 antibodies.
- Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF | Biological | MSC-NTF |
Primary outcome
Safety evaluation and tolerability of a single treatment administration in an escalating-dose of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF)
Time frame: At baseline and up to 6 month following treatment administration
5 secondary outcomes
Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale
Time frame: At baseline and up to 6 month following treatment administration
Changes in muscle strength grading (MVIC) by muscle chart
Time frame: At baseline and up to 6 month following treatment administration
Changes in muscle bulk estimated by MRI of the upper and lower extremities
Time frame: At baseline and up to 6 month following treatment administration
Change in upper and lower extremities circumference (cm)
Time frame: At baseline and up to 6 month following treatment administration
Changes in EMG parameters
Time frame: At baseline and up to 6 month following treatment administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2018.
- Derived from this study: PubMed 29116031Gothelf Y, Kaspi H, Abramov N, Aricha R. miRNA profiling of NurOwn(R): mesenchymal stem cells secreting neurotrophic factors. Stem Cell Res Ther. 2017 Nov 7;8(1):249. doi: 10.1186/s13287-017-0692-1.
- Derived from this study: PubMed 26751635Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, Vaknin-Dembinsky A, Ben-Hur T, Offen D, Abramsky O, Melamed E, Karussis D. Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. JAMA Neurol. 2016 Mar;73(3):337-44. doi: 10.1001/jamaneurol.2015.4321.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dimitrios Karusis, MD, PhD principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF in people with Amyotrophic Lateral Sclerosis, run by Brainstorm-Cell Therapeutics at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety evaluation and tolerability of a single treatment administration in an escalating-dose of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) (time frame: At baseline and up to 6 month following treatment administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01777646, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2018.